Pediatric Hematology and Oncology最新文献

Sickle cell anemia (SCA) is associated with a high prevalence of cerebrovascular complications, such as ischemic stroke, particularly at young ages. Among various molecules, vitamin D has been implicated in stroke occurrence. By binding to the vitamin D receptor (VDR), vitamin D regulates several mechanisms, potentially influencing pathways involved in the pathophysiology of cerebral vasculopathy. Here, we evaluated the association between VDR gene polymorphisms and 25-hydroxyvitamin D (25(OH)D) levels with CVD in a cohort of patients with SCA. The frequency of CVD and laboratory data were retrospectively obtained from the medical records. Genotyping for the functional FokI (rs2228570) and Cdx-2 (rs11568820) VDR polymorphisms was performed in 459 unrelated SCA patients. 25(OH)D levels were measured in a subset of 45 patients. The TT genotype of the FokI VDR polymorphism was associated with a higher frequency (OR: 2.82; 95% CI: 1.38-5.76, p = 0.006) and higher cumulative incidence (34% vs 16%, p = 0.001) of CVD compared to the other genotypes. Among patients under hydroxyurea (HU) therapy, individuals with the TT-FokI genotype (median: 13.9 ng/mL) had lower 25(OH)D levels compared to those with CC/CT genotypes (median: 20.2 ng/mL; p = 0.033). Similarly, patients with CVD and the TT-FokI genotype (median: 12.3 ng/mL) had reduced 25(OH)D levels compared to CC/CT carriers (median: 20.8 ng/mL; p = 0.034). These findings suggest that the FokI VDR polymorphism may serve as a potential genetic modulator of cerebrovascular complications in individuals with SCA.

The overall incidence of core binding factor acute myeloid leukemia (CBF-AML) in pediatric patients has been reported to be 19%-44.3%. However, the prognostic role of KIT mutations in pediatric CBF-AML remains controversial. This study aimed to investigate whether incorporating KIT mutation status into risk stratification improves long-term outcomes. A total of 114 pediatric CBF-AML patients treated under BCH-AML 2005 protocol and CCLG-AML 2015 protocol were enrolled. KIT mutations were identified using Sanger sequencing, classified as high-risk in CCLG-AML 2015. Relationships between clinical and biological features, outcomes and KIT mutations were evaluated across genetic subgroups. KIT mutations were identified in 25.4% pediatric CBF-AML, with comparable mutation rates in RUNX1::RUNX1T1 and CBFβ::MYH11 subgroups. Patients with KIT mutations showed higher leukemia burdens, including increased bone marrow blasts and white blood cell (WBC) indices. RUNX1::RUNX1T1 subgroup showed poorer 5-year OS than CBFβ::MYH11. Patients with KIT^mut17+ exhibited significantly lower OS, EFS compared to those with KIT^mut8+ and KIT^wt. Notably, RUNX1::RUNX1T1⁺KIT^mut17+ patients exhibited significantly worse OS among genetic subgroups but achieved improved OS under CCLG-AML 2015. KIT exon 17 mutational status and treatment protocol was identified as independent prognostic factors for OS and EFS in CBF-AML and RUNX1::RUNX1T1-AML. Our study found that prospective evaluation of KIT mutations is crucial in pediatric CBF-AML, particularly in RUNX1::RUNX1T1 patients, where the survival can be significantly improved by high-risk chemotherapy and hematopoietic stem cell transplantation.

Complementary medicine (CM) is commonly used by parents of pediatric cancer patients alongside conventional treatment, yet pediatric oncologists often feel inadequately trained to advise on CM. A collaborative project led by Gemeinschaftskrankenhaus Herdecke, integrated into inpatient pediatric cancer care in four centers in Germany in the Rhine-Ruhr Region, provides CM consultations and training for pediatric oncology teams. This study aimed to identify barriers perceived by healthcare professionals regarding the implementation of a CM advisory network for parents and assess their training needs. Eleven semi-structured interviews, lasting an average of 17.6 min, were conducted at four locations, including in-person (n = 7) and digital (n = 5) formats. Participants included physicians, senior physicians, residents and nurses. The interviews were analyzed using qualitative thematic analysis to inform targeted training for healthcare professionals to promote safe use of CM. The results highlighted the relevance of CM as perceived by healthcare professionals, as parents expect it to support their child's therapy. There was a notable interplay between parents' desire to explore options beyond conventional treatment and the stress they experience due to their child's diagnosis. The study identified necessary features for implementing a counseling service, emphasizing further training options, consistency, and identifying additional options. For team training, the interviewees stressed the importance of practical orientation and self-exploration. The key barriers identified were the scarcity of resources, including personnel, time, costs, and logistics. The study's findings will inform the development of future educational interventions for healthcare professionals.

Children with relapsed acute lymphoblastic leukemia (ALL) face higher rates of infection and treatment-related mortality than at initial diagnosis. Although immunotherapy is increasingly used in the relapsed setting, combination intensive chemotherapy remains the standard approach for reinduction. Serious infections during this phase can delay or preclude curative therapy. We aimed to describe the incidence and pattern of infections during reinduction in this high-risk population. In this single-center retrospective study, we reviewed charts of patients with relapsed ALL treated with combination chemotherapy reinduction at British Columbia Children's Hospital between 2006 and 2022. Forty-three patients were included (median age 10.2 years at relapse). Most (90%) received a standard four-drug reinduction. Median duration of severe neutropenia was 20.8 days. About half (51%) experienced at least one infection, including 16% with confirmed or probable fungal infection. Infection was associated with significantly longer hospitalization (median 17 vs. 7 days; p = 0.006). While no predictors reached statistical significance, hyperglycemia and neutropenia ≥ 21 days were associated with higher odds of infection. Overall survival did not differ significantly by infection status (log-rank p = 0.43). Infectious complications remain common during reinduction chemotherapy for relapsed ALL despite advances in supportive care. While pharmacologic and clinical strategies may reduce risk, safer and more targeted reinduction approaches are urgently needed to optimize outcomes in this vulnerable group.

Langerhans Cell Histiocytosis (LCH) is a rare histiocytic disorder that involves various organ systems. Recognizing gastrointestinal (GI) tract involvement in LCH is crucial, as GI cases, even without high-risk organ involvement, may be refractory to initial as well as second line therapy. Here, we report two cases of LCH with GI involvement, that were refractory to vinblastine, prednisone and cytarabine, and ultimately required clofarabine to reach clinical remission. We propose that clofarabine should be further studied as a first choice for second line treatment for GI-LCH cases and that GI involvement should be considered as high risk in the LCH risk stratification algorithm.

Intracardiac thrombus (ICT) in children is a serious and potentially life-threatening condition, particularly among hospitalized patients. Pediatric-specific data on ICT remain scarce, posing challenges for optimal, evidence-based management. This study aimed to analyze pediatric ICT cases over a decade to identify clinical characteristics, management strategies, and outcomes.

This retrospective study was conducted at a tertiary referral center and included all pediatric patients (ages 0-18) diagnosed with ICT between 2012 and 2023. Clinical and demographic data were extracted from electronic medical records, following IRB approval.

Twenty-three children were identified (median age: 39 months; 52% female). Major risk factors included central venous catheters (60.9%), congenital or acquired heart disease (52.2%), and malignancy (34.8%). Most thrombi (78.3%) were right-sided. ICT was incidentally diagnosed in 56.5% of cases; in others, symptoms led to imaging via echocardiography, CT, or cardiac catheterization.

Anticoagulation therapy was initiated in 87% of patients. Eight required indefinite treatment due to persistent thrombi or ongoing risk factors, while others received a median therapy duration of four months. Three patients did not receive anticoagulation due to clinical considerations. Surgical thrombectomy was performed in four cases (17.4%), and one patient underwent catheter-based thrombolysis. There were no major bleeding events. Complete thrombus resolution was achieved in 60.9% of cases, with partial improvement in 26.1%.

ICT in children is associated with identifiable risk factors and is commonly managed with anticoagulation. Surgical or interventional procedures may be needed in select cases. Early identification of high-risk patients is essential to improve outcomes.

Pain is the clinical hallmark of sickle cell disease (SCD), with painful Vaso-occlusive episodes (VOEs) being the common medical emergencies associated with an increased mortality rate. The current study aimed to evaluate the efficacy of L-arginine as an adjuvant therapy for children with SCD and VOE, as well as its effect on Tricuspid Regurgitant Jet Velocity (TRJV) during VOE. The primary outcome was to evaluate the efficacy of L-arginine on pain intensity. This double-blind, randomized, controlled, and parallel prospective study was carried out on 40 SCD children who presented with VOE and met the inclusion criteria. The mean ± SD of age was 8.8 ± 3.2 years, and 62.5% were males. They were randomized into two groups; Group 1 included 20 patients who received L-Arginine (100 mg/kg/dose three times/day for 15 doses or until their discharge) plus standard therapy. Group 2 consisted of 20 patients who received a placebo in addition to standard therapy. Total analgesic use, daily pain score, time to crisis resolution, and length of hospital stay were recorded. Routine laboratory investigations, serum L-Arginine, asymmetric dimethyl-arginine (ADMA) levels and the Arginine/ADMA ratio were assessed. Moreover, Echocardiography was performed to assess TRJV. All these parameters were assessed at baseline (during painful crisis), at discharge, and during the clinically asymptomatic state. As regards the age, sex, consanguinity, or family history there were no statistically significant difference between all of the studied groups. L-arginine therapy significantly decreased pain score at the 3rd day of admission(p-value 0.036), total analgesic use (p-value <0.001), time to crisis resolution (p-value 0.011), length of hospital stays (p-value 0.016), and TRJV (p-value < 0.001). Additionally, serum L-arginine level and Arginine/ADMA ratio (p-value <0.001) were increased upon arginine treatment. Additionally, statistically significant differences in the serum L-arginine level, serum ADMA level, Arginine/ADMA ratio, and TRJV were reported during painful crisis compared to the asymptomatic state. L-arginine Supplementation improved painful VOE symptoms in SCD children and decreased TRJV in those children. Oral arginine could be a promising adjuvant therapy for SCD-VOE management.

Cancer remains one of the leading causes of mortality among children worldwide. Both the disease itself and its treatment contribute to significant sleep-related issues. Pediatric cancer patients and survivors commonly experience sleep disturbances, including insomnia, excessive daytime sleepiness, prolonged sleep latency, reduced sleep duration, and poor overall sleep quality. The primary objective of this study was to assess the prevalence and characteristics of sleep disturbances in pediatric cancer patients and to compare these findings with those observed in children with non-oncologic conditions managed by the same pediatric oncology clinic. A secondary aim was to evaluate whether sleep disturbances in children affect the sleep quality of their caregivers. The study included 210 children aged 6 to 16 years and their caregivers. Diagnoses included lymphoma, solid tumors, Langerhans cell histiocytosis, neurofibromatosis, lymphadenopathy, and hemangioma. All participants were followed in our outpatient clinic between January 2 and May 25, 2023. Caregivers completed the Pittsburgh Sleep Quality Index (PSQI) to assess their own sleep quality and the Sleep Disturbance Scale for Children (SDSC) to evaluate their child's sleep patterns. The mean SDSC total score was 40.8 ± 8.1, indicating a high prevalence of sleep disturbances among children with cancer, particularly difficulties in initiating and maintaining sleep. The mean caregiver PSQI score was 5.02 ± 3.56. A moderate, statistically significant correlation was found between children's SDSC scores and their caregivers' PSQI scores (r = 0.433, p < 0.001). These findings underscore the importance of routine sleep assessments in pediatric oncology. Early recognition and management of sleep disturbances may enhance treatment adherence, improve therapeutic outcomes, and increase the overall quality of life for both patients and their caregivers.

This study aimed to explore how serum lipid levels are related to clinical features and outcomes in neuroblastoma(NB). We analyzed data from 169 patients diagnosed with NB, focusing on their serum lipid levels and how these relate to disease characteristics and prognosis. We found that older age (>18 months), high-risk disease features (e.g. elevated LDH, NSE, serum ferritin), genetic abnormalities (such as MYCN amplification, 1p36/11q23 LOH, PHOX2B expression), tumor size ≥10 cm, bone marrow metastasis, and multiple organ involvement were linked to abnormal lipid profiles, including elevated total cholesterol (TC), triglycerides (TG), LDL-C, and lipid ratios (TC/HDL-C, TG/HDL-C), along with reduced HDL-C. Interestingly, high TG and TG/HDL-C levels correlated with increased regulatory T cells (Tregs), which play a role in immune response. Patients with unfavorable lipid profiles-particularly high TC, TG, LDL-C, and lipid ratios or low HDL-C-had worse 5-year event-free survival (EFS) rates. This was especially true for high-risk patients. In statistical models, the TC/HDL-C ratio emerged as an independent predictor of poorer EFS. To assess lipid dynamics during treatment, we monitored patients at multiple time points and observed decreasing TC, TG, LDL-C, TC/HDL-C, and TG/HDL-C levels, alongside increasing HDL-C, suggesting treatment-induced improvement in lipid metabolism. In patients with disease progression or relapse, lipid levels (TC, LDL-C, HDL-C) were significantly elevated at the time of the event compared to post-chemotherapy levels.In summary, dysregulation of serum lipids is common in NB and lipid profiles are closely linked to NB progression and may serve as potential biomarkers for prognosis and treatment monitoring.

Pediatric patients with hematologic cancers, especially those undergoing chemotherapy, are highly vulnerable to infections and febrile neutropenia (FN). Noncompliance with FN protocols often leads to excessive antibiotic use, raising the risk of multidrug-resistant bacteria and contributing to higher mortality rates. This retrospective study aimed to assess inappropriate empirical antibiotic treatment (IEAT) rates during FN episodes and identify risk factors for mortality among pediatric patients diagnosed with acute leukemia and FN at the A.C. Camargo Cancer Center between January 1, 2010, and December 31, 2020. A total of 329 FN episodes in 84 patients were analyzed, revealing an overall IEAT rate of 40%. The study identified key issues such as 2% of inadequate Gram-positive coverage, 78% of failure to de-escalate antibiotic treatment and 62% of maintenance antibiotic administration despite negative cultures Bloodstream infections were found in 77% of episodes, with age over 13 years (p 0.003), and bloodstream infection (p 0.002) being significant risk factors for mortality.